The role of androgen in the normal and pathologic growth of the prostate gland is widely acknowledged but little understood. Evidence has accumulated pointing to the formation of 5 alpha-dihydrotestosterone (DHT) as an early and necessary step in the androgenic stimulation of target organs. In our previous work we have developed steroid inhibitors of DHT formation and have shown their antiandrogenic properties in the hamster flank organ test. We propose to continue these studies aimed at understanding the function of DHT as mediator of androgen action in the prostate gland as well as to develop useful inhibitors of its synthesis. Formation of DHT-protein complexes are also thought to be key events in the mechanism of tissue response to androgen stimulation. We have shown the presence of such DHT-binding proteins in transplantable prostatic tumors of Copenhagen rats which are androgen-sensitive (R-3327), but have not detected them in an androgen-insensitive line (R-3327-A). The loss of these receptors as a possible cause of the non-responsiveness of R-3327-A will be investigated. The receptor proteins will be isolated from the prostatic tumors and their physical and chemical properties studied in purified preparation. Measurements of the levels of androgen-binding proteins in human prostatic cancers will be carried out in cooperation with the Department of Urology. The levels detected will be correlated with the hormonal response of such cancers. These data hopefully will contribute to understand and predict why some cancers will respond to endocrine treatment while others will not. BIBLIOGRAPHIC REFERENCES: Walter Voigt and Mark Feldman. Hormone Dependency and Metabolism C57/BK Preputial Gland Adenocarcinoma. Proceedings of the V International Congress of Endocrinology, Hamburg, Germany, July 1976. (In Press). Mark Feldman, Walter Voigt and S.L. Hsia. A Steroid Binding Protein in Rat Preputial Gland Lysosomes. Proceedings of the V International Congress of Endocrinology, Hamburg, Germany, July 1976. (In Press).